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Cystatin C as a risk factor for outcomes in chronic kidney disease
Vandana Menon1, Michael G Shlipak, Xuelei Wang
1Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Insights
Cystatin C levels showed a risk for mortality and kidney failure in chronic kidney disease (CKD) patients, comparable to or stronger than serum creatinine and measured GFR. This highlights cystatin C as a valuable prognostic marker in CKD.
Area of Science:
- Nephrology
- Biomarkers
- Clinical Research
Background:
- Chronic kidney disease (CKD) risk factors for mortality and kidney failure are not well-established.
- No prior studies have compared cystatin C, serum creatinine, and estimated glomerular filtration rate (GFR) as risk factors in CKD patients.
Purpose of the Study:
- To compare cystatin C levels with serum creatinine and iothalamate GFR as predictors of death and kidney failure.
- To evaluate the prognostic value of different biomarkers in CKD.
Main Methods:
- An observational study utilizing baseline serum cystatin C samples from the Modification of Diet in Renal Disease Study (1989-1993).
- Included 825 participants with stage 3 or 4 non-diabetic CKD across 15 US clinical centers.
- Outcomes assessed included all-cause mortality, cardiovascular (CVD) mortality, and kidney failure over a median 10-year follow-up.
Main Results:
- Decreases in 1/creatinine, GFR, and 1/cystatin C were associated with increased risks for all-cause mortality, CVD mortality, and kidney failure.
- The risk increase for all-cause mortality per 1-SD decrease was 1.27 for 1/creatinine, 1.27 for GFR, and 1.41 for 1/cystatin C.
- For CVD mortality, risks increased by 1.32 (1/creatinine), 1.28 (GFR), and 1.64 (1/cystatin C); for kidney failure, risks increased by 2.81 (1/creatinine), 2.41 (GFR), and 2.36 (1/cystatin C).
Conclusions:
- Cystatin C's association with all-cause and CVD mortality was as strong as, or stronger than, iothalamate GFR in patients with stage 3 or 4 CKD.
- The study cohort may not represent all non-diabetic CKD patients, as they were more prone to kidney failure than death.
- Cystatin C is a valuable prognostic marker for adverse outcomes in CKD.
Background:
No study has compared cystatin C level, serum creatinine concentration, and estimated glomerular filtration rate (GFR) as risk factors for outcomes in chronic kidney disease (CKD), and none has compared measured GFR with CKD in any population.
Objective:
To compare cystatin C level with serum creatinine concentration and iothalamate GFR as risk factors for death and kidney failure.
Design:
Observational study using serum cystatin C assayed from baseline samples of the Modification of Diet in Renal Disease Study (1989-1993).
Setting:
15 clinical centers in the United States that participated in the Modification of Diet in Renal Disease Study.
Participants:
825 trial participants with stage 3 or 4 nondiabetic CKD who had measurements of serum cystatin C.
Measurements:
All-cause mortality, cardiovascular (CVD) mortality, and kidney failure until December 2000.
Results:
Mean cystatin C level, creatinine concentration, and GFR were 2.2 mg/L (SD, 0.7), 212.16 micromol/L (SD, 88.4) (2.4 mg/dL [SD, 1.0]), and 33 mL/min per 1.73 m2 (SD, 12), respectively. Median follow-up was 10 years. Twenty-five percent of patients (n = 203) died of any cause, 15% (n = 123) died of CVD, and 66% (n = 548) reached kidney failure. In multivariate-adjusted models, 1-SD decreases in 1/creatinine, GFR, and 1/cystatin C were associated with increased risks for all-cause mortality of 1.27 (95% CI, 1.06 to 1.49), 1.27 (CI, 1.08 to 1.49), and 1.41 (CI, 1.18 to 1.67), respectively. For CVD mortality, the increased risks were 1.32 (CI, 1.05 to 1.64), 1.28 (CI, 1.04 to 1.59), and 1.64 (CI, 1.28 to 2.08), respectively. For kidney failure, the increased risks were 2.81 (CI, 2.48 to 3.18), 2.41 (CI, 2.15 to 2.70), and 2.36 (CI, 2.10 to 2.66), respectively.
Limitation:
The Modification of Diet in Renal Disease Study cohort may not be representative of all patients with nondiabetic CKD because participants were more likely to reach kidney failure than death in follow-up.
Conclusion:
The association of cystatin C level with all-cause and CVD mortality was as strong as or perhaps stronger than that of iothalamate GFR with these outcomes in stage 3 or 4 CKD.
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